Researchers at the University of North Carolina (UNC) have developed microscopic flower-shaped soft robots made from DNA and inorganic materials that can fold, bend, and react to their environment. Detailed in a paper published in Nature Nanotechnology, these microscopic DNA “flowers” are a potential new method for targeted drug delivery and other biomedical applications.
“People would love to have smart capsules that would automatically activate medication when it detects disease and stops when it is healed. In principle, this could be possible with our shapeshifting materials,” said senior author Ronit Freeman, PhD, and associate professor at USC and leader of a research group that is seeking to develop novel designer materials using self-assembling biological components.
The DNA flowers are assembled from hybrid DNA, inorganic crystals that respond to environmental stimuli such as changes in acidity (pH), enabling reversible changes in shape—shrinking, bending, and folding—within seconds. The petals can open or close in response to local environmental conditions, motion that can be used to trigger a chemical reaction, release molecules, or interact with tissues.
The idea for these nanoscale shape-shifters was inspired by natural processes, such as the blooming of petals, the pulsing of coral, or the folding of tissues in biological organisms. “We take inspiration from nature’s designs, like blooming flowers or growing tissue, and translate them into technology that could one day think, move, and adapt on its own,” Freeman said.
To construct the flower-shaped actuators the team used a process called terminal deoxynucleotidyl transferase (TdT) DNA polymerization, which assembles DNA block copolymers within flower-shaped cobalt pyrophosphate crystals. By altering the sequence, length, and spatial arrangement of pH-sensitive (cytosine-rich) and inert (thymine-rich) DNA segments, the researchers can program how the flower responds.
For instance, “in response to acidic environments, interspersed C-blocks adopt an i-motif configuration, thereby acting as molecular springs instructing flowers to reversibly shrink/swell or close/open,” the researchers wrote.
These structural transformations can occur in a range size, from nanometer-sized DNA to micrometer-sized crystals, allowing the researchers to tailor mechanical control of these structures based on their applications. The DNA within the flower provides a method for the compartmentalization of biochemical reactions, allowing it to store and then activate enzyme cascades or release payloads like proteins, nucleic acids, or small molecules in response to environmental signals.
In the biomedical context, the DNA flowers could be designed to respond to the acidic microenvironment of tumors or sites of infection. The flowers could carry a drug payload that is only released when the petals sense and respond to a low pH environment, then could deactivate once normal conditions return. This precision delivery of drug dose has potential to minimize off-target effects of medications while delivering only the required doses needed for treatment.
Noting the broad potential of this new platform, Freeman noted that “in the future, swallowable or implantable shape-changing flowers could be designed to deliver a targeted dose of drugs, perform a biopsy, or clear a blood clot.”
This new research builds on previous work focused on DNA–inorganic nanoflowers, which have been used for imaging and drug delivery but did not have the capability for mechanical actuation. Other research efforts concentrated on creating flexible biomaterials have focused on the use of hydrogels and polymers to allow for shape changing, but these designs didn’t allow for the programmability of the new DNA flowers.
Ongoing work at UNC will look to make this new system responsive to additional stimuli, such as light. With compatibility for various payloads and the ability to operate autonomously at small scales, these DNA–inorganic flowers have significant potential to allow for the development of novel drug delivery systems, soft robotics, or smart implants that respond precisely to physiological conditions.
